5-Nitro-2-[2-[8-[2-(5-nitro-1,3-dioxobenzo[de]isoquinolin-2-yl)ethyl]-3,8-diazabicyclo[3.2.1]octan-3-yl]ethyl]benzo[de]isoquinoline-1,3-dione | 1123690-78-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 5-Nitro-2-[2-[8-[2-(5-nitro-1,3-dioxobenzo[de]isoquinolin-2-yl)ethyl]-3,8-diazabicyclo[3.2.1]octan-3-yl]ethyl]benzo[de]isoquinoline-1,3-dione
• CAS: 1123690-78-7
• 化学式: C₃₄H₂₈N₆O₈
• 分子量: 648.632
• InChiKey: LZNCTXBZYKCTIY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  48
• 可旋转键数：
  6
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  173
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  3,8-bis(aminomethyl)-3,8-diazabicyclo[3.2.1]octane 、 3-硝基-1,8-萘二甲酸酐 以 乙醇 、 甲苯 为溶剂， 反应 4.0h， 以83%的产率得到5-Nitro-2-[2-[8-[2-(5-nitro-1,3-dioxobenzo[de]isoquinolin-2-yl)ethyl]-3,8-diazabicyclo[3.2.1]octan-3-yl]ethyl]benzo[de]isoquinoline-1,3-dione
  参考文献：
  名称：

  Molecular modelling studies, synthesis and biological activity of a series of novel bisnaphthalimides and their development as new DNA topoisomerase II inhibitors

  摘要：

  A series of bisnaphthalimide derivatives were synthesized and evaluated for growth-inhibitory property against HT-29 human colon carcinoma. The N, N '-bis[2-(5-nitro-1,3-dioxo-2,3-dihydro-1H-benz[de]-isoquinolin-2-yl)] propane-2-ethanediamine (9) and the N, N '-Bis[2-(5-nitro-1,3-dioxo-2,3-dihydro-1H-benz[de]-isoquinolin-2-yl)] butylaminoethyl]-2-propanediamine (12) derivatives emerged as the most potent compounds of this series. Molecular modelling studies indicated that the high potency of 12, the most cytotoxic compound of the whole series, could be due to larger number of intermolecular interactions and to the best position of the naphthalimido rings, which favours pi-pi stacking interactions with purine and pyrimidine bases in the DNA active site. Moreover, 12 was designed as a DNA topoisomerase II poison and biochemical studies showed its effect on human DNA topoisomerase II. We then selected the compounds with a significant cytotoxicity for apoptosis assay. Derivative 9 was able to induce significantly apoptosis (40%) at 0.1 mu M concentration, and we demonstrated that the effect on apoptosis in HT-29 cells is mediated by caspases activation. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.11.024

文献信息

• Molecular modelling studies, synthesis and biological activity of a series of novel bisnaphthalimides and their development as new DNA topoisomerase II inhibitors
  作者：Rosanna Filosa、Antonella Peduto、Simone Di Micco、Paolo de Caprariis、Michela Festa、Antonello Petrella、Giovanni Capranico、Giuseppe Bifulco

  DOI：10.1016/j.bmc.2008.11.024

  日期：2009.1

  A series of bisnaphthalimide derivatives were synthesized and evaluated for growth-inhibitory property against HT-29 human colon carcinoma. The N, N '-bis[2-(5-nitro-1,3-dioxo-2,3-dihydro-1H-benz[de]-isoquinolin-2-yl)] propane-2-ethanediamine (9) and the N, N '-Bis[2-(5-nitro-1,3-dioxo-2,3-dihydro-1H-benz[de]-isoquinolin-2-yl)] butylaminoethyl]-2-propanediamine (12) derivatives emerged as the most potent compounds of this series. Molecular modelling studies indicated that the high potency of 12, the most cytotoxic compound of the whole series, could be due to larger number of intermolecular interactions and to the best position of the naphthalimido rings, which favours pi-pi stacking interactions with purine and pyrimidine bases in the DNA active site. Moreover, 12 was designed as a DNA topoisomerase II poison and biochemical studies showed its effect on human DNA topoisomerase II. We then selected the compounds with a significant cytotoxicity for apoptosis assay. Derivative 9 was able to induce significantly apoptosis (40%) at 0.1 mu M concentration, and we demonstrated that the effect on apoptosis in HT-29 cells is mediated by caspases activation. (c) 2008 Elsevier Ltd. All rights reserved.